• Journal of Korean Neurosurgical Society
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• 제59권3호
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• pp.259-268
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• 2016

Objective : Accumulation of advanced glycation end-products (AGE) and mitochondrial glycation is importantly implicated in the pathological changes of the brain associated with diabetic complications, Alzheimer disease, and aging. The present study was undertaken to determine whether sildenafil, a type 5 phosphodiesterase type (PDE-5) inhibitor, has beneficial effect on neuronal cells challenged with AGE-induced oxidative stress to preserve their mitochondrial functional integrity. Methods : HT-22 hippocampal neuronal cells were exposed to AGE and changes in the mitochondrial functional parameters were determined. Pretreatment of cells with sildenafil effectively ameliorated these AGE-induced deterioration of mitochondrial functional integrity. Results : AGE-treated cells lost their mitochondrial functional integrity which was estimated by their MTT reduction ability and intracellular ATP concentration. These cells exhibited stimulated generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, induction of mitochondrial permeability transition, and release of the cytochrome C, activation of the caspase-3 accompanied by apoptosis. Western blot analyses and qRT-PCR demonstrated that sildenafil increased the expression level of the heme oxygenase-1 (HO-1). CoPP and bilirubin, an inducer of HO-1 and a metabolic product of HO-1, respectively, provided a similar protective effects. On the contrary, the HO-1 inhibitor ZnPP IX blocked the effect of sildenafil. Transfection with HO-1 siRNA significantly reduced the protective effect of sildenafil on the loss of MTT reduction ability and MPT induction in AGE-treated cells. Conclusion : Taken together, our results suggested that sildenafil provides beneficial effect to protect the HT-22 hippocampal neuronal cells against AGE-induced deterioration of mitochondrial integrity, and upregulation of HO-1 is involved in the underlying mechanism.

• Journal of Korean Neurosurgical Society
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• 제47권3호
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• pp.210-212
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• 2010

Sildenafil citrate ($Viagra^{(R)}$ Pfeizer US Pharmaceutical Group, New York, NY, USA) is a potent vasodilating agent to treat male erectile dysfunction. Among its adverse effects, hemorrhagic stroke has not been widely reported yet. We present a case of a 33-year-old healthy man who ingested 50 mg sildenafil a half hour before onset of headache, nervousness and speech disturbance. Head computed tomogram of this stuporous man showed huge intracerebral hemorrhage and thick subarachnoid hemorrhage, but angiography failed to disclose any vascular anomalies. Subsequent surgical procedure was followed, and rehabilitation was provided thereafter. Sildenafil seems to act by redistributing arterial blood flow, and concurrent sympathetic hyperactivity, which lead to such hemorrhagic presentation. Extreme caution should be paid on even in a young adult male patient wven without known risk factors.

• 한국식품위생안전성학회지
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• 제29권2호
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• pp.92-98
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• 2014

경기도내 유통되고 있는 발기부전치료제 유사제품 51건(유사비아그라 26품목, 유사시알리스 25품목)에 대하여 발기부전치료제성분 및 그 유사물질을 조사하여 안전성을 평가하였다. 발기부전치료제성분 4종과 그 유사물질 17종에 대하여 HPLC/PDA, LC-MS/MS를 이용하여 정량 및 정성시험을 실시하였다. 유사비아그라의 경우에는 sildenafil 성분이 40~199 mg/정의 범위를 나타냈으며, 함량이 150 mg/정 넘는 제품이 65% 이상 이었다. Tadalafil과 sildenafil을 동시에 사용한 경우는 3개 제품에서 나타났다. 유사시알리스의 경우에는 주성분인 tadalafil이 모두 검출되지 않았고 비아그라의 주성분인 sildenafil만 102 mg/정~249 mg/정 검출되었다. 이 중 sildenafil 함량이 150 mg/정 넘는 제품이 88% 이상 이었으며, 1개 제품에서 발기부전치료제유사물질인 demethylhongdenafil이 90 mg/정 검출되었다. 이러한 발기부전치료제 유사제품은 권장 복용량보다 3배가 넘는 고 함량 제품이 대부분이었으며, 지속적인 감시와 유통차단이 요구된다고 본다.

• Clinical and Experimental Pediatrics
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• 제59권6호
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• pp.262-270
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• 2016

Purpose: Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF. Methods: The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed. Results: The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-${\alpha}$, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4. Conclusion: Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function.

• 한국식품위생안전성학회지
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• 제18권4호
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• pp.195-201
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• 2003

본 연구에서는 국내 ${\cdot}$ 외에서 유통되는 건강관련식품 중 성기능 개선 및 효과에 대하여 광고 ${\cdot}$ 판매하고 있는 제품들에 대하여 최근 의약품으로 허가된 발기부전치료제인 sildenafil, vardenafil, tadalafil 및 sildenafil의 유사물질인 homosildenafil을 대상으로 정성과 정량을 위한 동시분석법을 개발하고 유통 제품 중의 함량을 분석하여 함유 실태를 파악하고자 하였다. 네 가지 성분을 확인할 수 있는 TLS와 LC/MS 분석방법을 개발하였으며, LC/PDA를 사용한 동시 정량분석법을 개발하고, 건강보조식품 등 건강관련 식품중 sildenafil 등 4종 물질에 대해 총 35개의 시료를 분석한 결과 sildenafil이 7종에서 0.4 mg/g~360.9 mg/g, homosildenafil이 7종에서 2.2 mg/g~336.0 mg/g, tadalafid이 2종에서 각각 19.2mg/g, 429.3mg/g로 검출되었으며, 본 여구에서 개발한 동시분석법을 유통식품에 적용 가능하였다.

• 대한화학회지
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• 제54권4호
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• pp.443-446
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• 2010

기능성식품으로 시판되는 건강음료를 HPLC 분석한 결과 발기부전치료제로 허가받은 비아그라$^{(R)}$의 활성주성분인 실데나필과 구조적으로 유사한 부정첨가물질이 발견되었다. 이 부정첨가물질의 구조를 규명하기 위해 건강음료를 methylene chloride로 추출한 다음 그 추출물을 semipreparative HPLC로 정제하였다. 분리된 물질의 화학구조는 IR, LC/MS-ESI, NMR 분광학으로 규명하였는데 실데나필과 유사한 특징을 보였고 구조상의 유일한 차이는 실데나필의 methylpiperazine 부분구조를 부정첨가물질에서 hydroxyethylpiperazine으로 치환한 것이었다.

• Biomolecules & Therapeutics
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• 제11권4호
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• pp.232-237
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• 2003

The present study examined functional effects of a new selective phosphodiesterase type 5 inhibitor, 1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-thioxo-3-propyl-1H-pyrazolo[ 4,3]pyrimidin-5-yl)phenylsulphonyl]-4-methyl piperazine (KJH-1002), in the isolated rabbit corpus cavernosum (RCC). Relaxing effects of KJH-1002 were also compared with those of sildenafil, which is currently used as an oral therapy for penile erectile dysfunction. In the isolated RCC precontracted with phenylephrine, both KJH-1002 and sildenafil in the concentration range of 1 to 1000 nM, produced a comparable potentiation of the electical field stimulation-induced relaxation in a concentration-dependent manner. In the sodium nitroprusside (SNP)-induced relaxation, the $IC_{50}$/ values, concentrations of SNP required to produce a 50％ relaxation of the phenylephrine-induced contraction, were significantly decreased to the similar extent by treatments with KJH-1002 and sildenafil. The results suggest that a new selective phosphodiesterase type 5 inhibitor, KJH-1002, has an augmentative effect on penile erection comparable to that of sildenafil and can be useful for the treatment of erectile dysfunction.

• 한국식품위생안전성학회:학술대회논문집
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• 한국식품위생안전성학회 2004년도 제3회 식품안전의 날 기념 학술 세미나
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• pp.49-68
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• 2004

New analogues of Sildenafil (Viagra${\circledR}$)were identified in the imported Chinese herb drinks, which have been added illegally for affecting penile erectile dysfunction. In order to elucidate the chemical structures of Sildenafil analogues, separation and purification were carried out and followed by analysis of the routine 1D and 2D NMR spectroscopy and FAB mass spectrometry. Based on analytical data one compound was maned as Homosildenafil contains ethylpiperazine switched with methylpiperazine of Sildenafil and the other one was called an Hongdenafil contains ethylpiperazine switched with methylpiperazine and acetyl group instead of sulfonyl group of Sildenafil. As results, Homosildenafil and Hongdenafil were put on the list as new inspection items of the imported food for protectiong public health in Korea.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.396.1-396.1
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• 2002

HPTLC(High Performance Thin Layer Choromatography) method was developed for rapid and precise analysis of Sildenafil and modified Sildenafils(Vardenafil. Homosildenafil, Tadanafil). Chromatographic conditions were Optimized for simultaneous analysis of them and each specific UV spectra were obtained. The calibration curve of Sildenafil and modified Sildenafils had a linearity in the range of 1.0 ~ 56.5 $\mu$/ml at 254nm. The Limit of Detection(LOD) and the limit of Quantification(LOQ) of Sildenafil and modified Sildenafils were 0.8$\mu$/ml and 1.0$\mu$g/ml. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제10권3호
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• pp.149-154
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• 2006

Selective inhibition of phosphodiesterase (PDE) 5 opened a new therapeutic approach for cardiovascular disorders. Therefore, the effect of PDE5 inhibition on the cardiac function should thoroughly be defined. The purpose of the present study was to define the effects of sildenafil, a selective inhibitor of PDE5, on the atrial cGMP efflux, atrial dynamics, and the release of atrial natriuretic peptide (ANP). By perfusing rabbit left atria to allow atrial pacing, changes in atrial stroke volume and pulse pressure, transmural extracellular fluid translocation, cGMP efflux, and ANP secretion were measured. SIN-I, an NO donor and soluble (s) guanylyl cyclase (GC) activator, and C-type natriuretic peptide (CNP), an activator of particulate (p) GC activator, were used. Sildenafil increased basal levels of cGMP efflux slightly but not significantly. Sildenafil in a therapeutic dose increased atrial dynamics (for atrial stroke volume, $2.84{\pm}1.71%$, n=12, vs $-0.71{\pm}0.86%$, n=21; p<0.05) and decreased ANP release ($-9.02{\pm}3.36%$, n=14, vs $1.35{\pm}3.25%$, n=23; p < 0.05), however, it had no effect on the SIN-1- or CNP-induced increase of cGMP levels. Furthermore, sildenafil in a therapeutic dose accentuated SIN-1-induced, but not CNP-induced, decrease of atrial pulse pressure and ANP release. These data indicate that PDE5 inhibition with sildenafil has a minor effect on cGMP levels, but has a distinct effect on pGC-cGMP- and sGC-cGMP-induced contractile and secretory function.